PMID- 38084656
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240318
IS  - 2163-8306 (Electronic)
IS  - 2163-8306 (Linking)
VI  - 13
IP  - 3
DP  - 2024 Mar
TI  - Supplementing clinical lactation studies with PBPK modeling to inform drug 
      therapy in lactating mothers: Prediction of primaquine exposure as a case 
      example.
PG  - 386-395
LID - 10.1002/psp4.13090 [doi]
AB  - Evaluating the safety of primaquine (PQ) during breastfeeding requires an 
      understanding of its pharmacokinetics (PKs) in breast milk and its exposure in 
      the breastfed infant. Physiologically-based PK (PBPK) modeling is primed to 
      assess the complex interplay of factors affecting the exposure of PQ in both the 
      mother and the nursing infant. A published PBPK model for PQ describing the 
      metabolism by monoamine oxidase A (MAO-A; 90% contribution) and cytochrome P450 
      2D6 (CYP2D6; 10%) in adults was applied to predict the exposure of PQ in mothers 
      and their breastfeeding infants. Plasma exposures following oral daily dosing of 
      0.5 mg/kg in the nursing mothers in a clinical lactation study were accurately 
      captured, including the observed ranges. Reported infant daily doses based on 
      milk data from the clinical study were used to predict the exposure of PQ in 
      breastfeeding infants greater than or equal to 28 days. On average, the predicted 
      exposures were less than or equal to 0.13% of the mothers. Furthermore, in 
      simulations involving neonates less than 28 days, PQ exposures remain less than 
      0.16% of the mothers. Assuming that MAO-A increases slowly with age, the 
      predicted relative exposure of PQ remains low in neonates (<0.46%). Thus, the 
      findings of our study support the recommendation made by the authors who reported 
      the results of the clinical lactation study, that is, that when put into context 
      of safety data currently available in children, PQ should not be withheld in 
      lactating women as it is unlikely to cause adverse events in breastfeeding 
      infants greater than or equal to 28 days old.
CI  - (c) 2023 Certara UK. CPT: Pharmacometrics & Systems Pharmacology published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Pan, Xian
AU  - Pan X
AUID- ORCID: 0000-0003-2418-5970
AD  - Certara UK Limited (Simcyp Division), Sheffield, UK.
FAU - Abduljalil, Khaled
AU  - Abduljalil K
AUID- ORCID: 0000-0003-0725-9237
AD  - Certara UK Limited (Simcyp Division), Sheffield, UK.
FAU - Almond, Lisa M
AU  - Almond LM
AUID- ORCID: 0000-0002-6684-4287
AD  - Certara UK Limited (Simcyp Division), Sheffield, UK.
FAU - Pansari, Amita
AU  - Pansari A
AUID- ORCID: 0000-0002-7163-2633
AD  - Certara UK Limited (Simcyp Division), Sheffield, UK.
FAU - Yeo, Karen Rowland
AU  - Yeo KR
AUID- ORCID: 0000-0002-7020-1970
AD  - Certara UK Limited (Simcyp Division), Sheffield, UK.
LA  - eng
PT  - Journal Article
DEP - 20231212
PL  - United States
TA  - CPT Pharmacometrics Syst Pharmacol
JT  - CPT: pharmacometrics & systems pharmacology
JID - 101580011
RN  - MVR3634GX1 (Primaquine)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
SB  - IM
MH  - Infant
MH  - Infant, Newborn
MH  - Adult
MH  - Child
MH  - Female
MH  - Humans
MH  - *Lactation/metabolism
MH  - *Primaquine/metabolism
MH  - Mothers
MH  - Breast Feeding
MH  - Cytochrome P-450 CYP2D6/metabolism
MH  - Monoamine Oxidase
PMC - PMC10941563
COIS- All author are employees of Certara UK Limited (Simcyp Division) and may hold 
      shares in Certara. As Deputy Editor in Chief of CPT: Pharmacometrics & Systems 
      Pharmacology, Karen Rowland Yeo was not involved in the review or decision 
      process for this paper.
EDAT- 2023/12/12 06:42
MHDA- 2024/03/18 06:42
PMCR- 2023/12/12
CRDT- 2023/12/12 05:42
PHST- 2023/10/28 00:00 [revised]
PHST- 2023/07/30 00:00 [received]
PHST- 2023/11/20 00:00 [accepted]
PHST- 2024/03/18 06:42 [medline]
PHST- 2023/12/12 06:42 [pubmed]
PHST- 2023/12/12 05:42 [entrez]
PHST- 2023/12/12 00:00 [pmc-release]
AID - PSP413090 [pii]
AID - 10.1002/psp4.13090 [doi]
PST - ppublish
SO  - CPT Pharmacometrics Syst Pharmacol. 2024 Mar;13(3):386-395. doi: 
      10.1002/psp4.13090. Epub 2023 Dec 12.